Faculty Bibliography

ABSTRACT: BACKGROUND: Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD). This analysis aimed to evaluate the impact of lisdexamfetamine dimesylate (LDX) on sleep quality in adults with ADHD. METHODS: This 4-week, phase 3, double-blind, forced-dose escalation study of adults aged 18 to 55 years with ADHD randomized participants to receive placebo (n = 62), or 30 (n = 119), 50 (n = 117), or 70 (n = 122) mg/d LDX, taken once a day in the morning. The self-rated Pittsburgh Sleep Quality Index (PSQI) was administered at baseline and at week 4 to assess sleep quality. The PSQI global score assesses 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) each scored from 0 (no difficulty) to 3 (severe difficulty). RESULTS: The mean baseline PSQI global score was 5.8 for LDX and 6.3 for placebo (P = .19) indicating poor overall sleep quality. At endpoint, least squares (LS) mean change from baseline was -0.8 for LDX vs -0.5 for placebo (P = .33). The daytime functioning component showed significant improvement in LS mean change at endpoint for LDX compared with placebo (LDX -0.4 vs placebo 0.0, P = .0001). LS mean changes for the other 6 PSQI components did not significantly differ from placebo. Sleep-related treatment-emergent adverse events with an incidence >/=2% in the active treatment and placebo groups, respectively, were insomnia (19.3% and 4.8%), initial insomnia (5.0% and 3.2%), middle insomnia (3.6% and 0%), sleep disorder (0.6% and 3.2%), somnolence (0.3% and 3.2%), and fatigue (4.7% and 4.8%), and were generally mild or moderate in severity. CONCLUSION: For most subjects, LDX was not associated with an overall worsening of sleep quality and significantly improved daytime functioning in adults with ADHD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00334880

Introduction: The objective of this article is to compare primary care physicians' (POPs') experiences with diagnosing and treating adult attention-deficit/hyperactivity disorder (ADHD) versus other mental health disorders. Methods: Four hundred PCPs who have patients with ADHD, bipolar disorder, depression, generalized anxiety disorder (GAD), or obsessive-compulsive disorder completed a public release survey assessing their experiences and attitudes on diagnosing and treating these disorders. Results: Forty-eight percent of PCPs felt uncomfortable diagnosing adult ADHD and 44% reported that there were no clear diagnostic criteria. Seventy-five percent rated the quality and accuracy of existing adult ADHD diagnostic tools as either poor or fair. Seventy-two percent reported that ADHD is easier to diagnose in children than adults. Sixty-five percent reported deferring to specialists to diagnose adult ADHD, compared to 2% for depression and 3% for GAD. Eighty-five percent reported that they would be more comfortable diagnosing and treating adult ADHD if thorough, straightforward screening tools were validated and if there were effective medications that were neither stimulants nor controlled substances. Discussion: While this survey indicated that adult ADHD is generally accepted by PCPs, the results also indicate that PCPs are significantly less likely to diagnose and treat ADHD in adults without deferring to a specialist, when compared to GAD and depression. The recent development of new screening tools for adult ADHD as well as non-stimulant and novel stimulant medications may reduce PCPs' reliance on specialist referrals. Conclusion: This study highlights a potential need for PCPs for increased education and training in adult ADHD. As the study was conducted 6 years ago, follow-up investigations into the current PCP awareness of adult ADHD are indicated.

BACKGROUND: Although attention deficit/hyperactive disorder (ADHD) is a common comorbidity in individuals who are diagnosed with substance use disorder (SUD), little data currently exist on the utility of screening tools in large samples of adults with SUD in inpatient treatment and the prevalence of ADHD in this population. The aims of this study were to assess the screen positive rate on the Adult ADHD Self Report Scale (ASRS) v.1.1 Screener in a large sample of adults being treated for SUD in a residential treatment facility (RTF) and to establish the imputed prevalence of adult ADHD. METHODS: Adults with SUD who were either newly admitted (abstinent for < 1 week) or in treatment in the RTF (abstinent < 3 months) were administered the ASRS v.1.1 Screener. Adults who screened positive on the ASRS v1.1 Screener (>or= 4/6 significant items) were then administered the Adult Clinician Diagnostic Scale (ACDS) v.1.2 to establish a diagnosis of ADHD and the positive predictive value (PPV) in this population. The imputed prevalence of adult ADHD was calculated based on the known rate of ADHD in the screened positive cohort and a calculated rate of ADHD in the screened negative sample based on prior studies of the ASRS v1.1 Screener in community-based and managed care samples. RESULTS: 1064 adults were screened via the ASRS v.1.1 Screener, with 92 screening positive (8.6% had >or= 4 significant items present). Fifty-three of those who screened positive were diagnosed as having adult ADHD (PPV = 57.6%). The imputed prevalence of adult ADHD in this population was 7.5%. CONCLUSIONS: The PPV for the ASRS v1.1 Screener for adult ADHD in this sample of adults with SUD was similar to that observed in a prior study of a managed care sample, but was somewhat less than that observed in the community-based sample. The imputed prevalence rate for comorbid ADHD in this study of adults with SUD in a RTF was similar to, but slightly lower than the prevalence rate of ADHD in patients with any SUD observed in the community-based sample

This post hoc analysis compared the safety of atomoxetine treatment of ADHD in adults with or without comorbid alcohol abuse/dependence. Study completion rates in patients receiving atomoxetine were comparable between heavy drinkers (60.9%) and patients with no alcohol-use disorder (71.0%) but lower in nonheavy drinkers (35.7%); however, there was no significant difference in discontinuation rates due to adverse events or lack of efficacy among these groups. Alcohol-use disorder patients, especially heavy drinkers, generally experienced the greatest frequency of treatment-emergent adverse events in both the atomoxetine and placebo groups. Vital signs and measures of hepatic function were not significantly different among the 3 drinking status groups taking atomoxetine

OBJECTIVE: The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy. METHOD: 276 patients with major depressive disorder (MDD) were treated with sertraline (150-200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy. RESULTS: The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. CONCLUSION: This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials

OBJECTIVE: To evaluate the short-term impact of lisdexamfetamine dimesylate on cardiovascular parameters in adults with attention-deficit/hyperactivity disorder (ADHD). METHOD: Medically healthy adults (18-55 years of age) with DSM-IV-TR-defined ADHD were randomly assigned to placebo or 30, 50, or 70 mg/d of lisdexamfetamine dimesylate for 4 weeks between May and November 2006. Electrocardiograms, systolic and diastolic blood pressure, and pulse were assessed pretreatment and weekly thereafter. RESULTS: There were no significant differences for mean systolic or diastolic blood pressure in any lisdexamfetamine dimesylate dose group versus placebo. Changes in pulse from baseline to endpoint were 0.0, 2.8, 4.2, and 5.2 bpm in the placebo and lisdexamfetamine dimesylate 30, 50, and 70 mg/d groups, respectively (P < .05, all lisdexamfetamine dimesylate groups vs placebo). Post hoc pulse outliers (pulse > or = 100 bpm; any 1 event) ranged from 3.3% to 8.5% of subjects in the lisdexamfetamine dimesylate groups, and no subjects in the placebo group were pulse outliers (P < .05 for lisdexamfetamine dimesylate 50 mg vs placebo only). There were no clinically meaningful electrocardiogram abnormalities. Overall, 8.3% (35/420; safety population) of subjects had treatment-emergent cardiovascular adverse events, and 1.7% (7/420) withdrew from the study because of cardiovascular complaints. Cardiovascular adverse events with lisdexamfetamine dimesylate in these medically healthy adults were generally mild to moderate in severity. CONCLUSIONS: Lisdexamfetamine dimesylate had limited short-term effects on heart rate, blood pressure, and electrocardiogram parameters that were of minimal clinical concern. These findings support the relative safety of lisdexamfetamine dimesylate. However, considering the potential of outliers, it is advisable to monitor cardiovascular parameters in stimulant-treated patients. Interpretation of these findings is limited to patients with no preexisting cardiac conditions who are taking their medication as prescribed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00334880

OBJECTIVE: Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed and prescribed stimulant medications in adolescent and young adult populations. The purpose of this systematic review of the literature is to evaluate the extent and characteristics of stimulant misuse and diversion in attention-deficit/hyperactivity disorder (ADHD) and non-ADHD individuals. METHOD: We conducted a systematic review of the literature of available studies looking at misuse and diversion of prescription ADHD medications using misuse, diversion, stimulants, illicit use, and ADHD medications as key words for the search. RESULTS: We identified 21 studies representing 113,104 subjects. The studies reported rates of past year nonprescribed stimulant use to range from 5% to 9% in grade school- and high school-age children and 5% to 35% in college-age individuals. Lifetime rates of diversion ranged from 16% to 29% of students with stimulant prescriptions asked to give, sell, or trade their medications. Recent work suggests that whites, members of fraternities and sororities, individuals with lower grade point averages, use of immediate-release compared to extended-release preparations, and individuals who report ADHD symptoms are at highest risk for misusing and diverting stimulants. Reported reasons for use, misuse, and diversion of stimulants include to concentrate, improve alertness, 'get high,' or to experiment. CONCLUSIONS: The literature suggests that individuals both with and without ADHD misuse stimulant medications. Recent work has begun to document the context, motivation, and demographic profile of those most at risk for using, misusing, and diverting stimulants. The literature highlights the need to carefully monitor high-risk individuals for the use of nonprescribed stimulants and educate individuals with ADHD as to the pitfalls of the misuse and diversion of the stimulants